It is generally believed that two independent stages known as initiation and promotion participate in chemical carcinogenesis. This theory, known as the two-stage theory of carcinogenesis, was proposed by Berenblum in Cancer Res., 1, 807-814 (1941). The initiation stage is an irreversible reaction in which a chemical material known as an initiator induces a DNA change. The most widely known initiator is dimethylbenzanthracene (DMBA).
The next stage is the promotion stage in which a chemical material known as a promoter leads cells to eventual canceration. Among carcinogenesis promoters, croton oil extracted from croton seeds or its predominant ingredient, 12-O-tetradecanoylphorbol 13-acetate (TPA) is known to be highly active. At present, there have been found in the environment a number of carcinogenesis promoters having different chemical structures from TPA. Among these promoters, some act in the same mechanism as TPA (TPA type promoters) and some act in a different mechanism from TPA (non-TPA type promoters).
Recently, it was discovered that bile acids and hormones which are biological products can become promoters. It has been and will be discovered that many familiar substances can be carcinogenesis promoters as exemplified by the discovery that sodium chloride can be a gastric carcinoma promoter.
There is a need for the development of a novel carcinostatic agent capable of restraining carcinogenesis promotion an controlling carcinoma.